Background Nipah virus (NiV) is 1 of 10 potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in 2 human survivors. Methods Serial blood samples were obtained from the only 2 survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T-lymphocyte and B-lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. More than 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B-lymphocyte, activated B-cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells. Conclusions We describe for the first time longitudinal kinetic data on the activation status of human B- and T-cell populations during acute NiV infection. While marked CD8 T-cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.
Hip fractures in elderly are commonly associated with osteoporosis and surgical outcome is influenced by its concurrent management. The purpose of our study is to determine the association between timing of bisphosphonate administration in inter-trochanteric (IT) fractures and fracture healing. Patients with IT fractures (aged!50 years) and T-score -1.5 [WHO defines osteopenia as T-score between À1 and À2.5, and osteoporosis as T-score -2.5 on DEXA scan (which was obtained post-operatively in our cohort)], who underwent proximal femoral nailing were included. Patients were divided into three groups: group 1a-intravenous bisphosphonate {ivBP [zoledronic acid (ZA)]} given within one week, group 1b-ZA at six weeks and group 2-control group. Post-operative radiographs were assessed for reduction parameters [neck-shaft angle, tip-apex distance, reduction variance]. Radiological union was determined using RUSH score and functional outcome (at one year) with Modified Harris Hip Scores. 41 (23 males), 40 (15 males) and 42 (15 males) patients were included in groups 1a, 1b and 2, respectively (no statistical difference in sex distribution among the groups; p ¼ 0.12). Mean age in groups 1a, 1b and 2 was 71.8 ± 8.1, 75.9 ± 8.5 and 72.3 ± 10.6 years (p ¼ 0.09). There was no significant difference in the pattern of injuries (AO classification) among the groups (p ¼ 0.72). Mean time to union in groups 1a, 1b and 2 was 13.7,13.7 and 14.2 weeks, respectively (p ¼ 0.69). Mean time to union in AO types A1, A2 and A3 fractures was 13.2 ± 2.1, 13.7 ± 2.8 and 16.1 ± 4.9 weeks (p ¼ 0.01). We did not observe any association between T-scores and fracture union (hip:p ¼ 0.52, spine:p ¼ 0.93).The functional outcome was similar among groups (p ¼ 0.96). Early administration of ZA did not negatively influence fracture healing in patients undergoing fixation of IT fractures. Among the various other factors analyzed, there was a statistically significant association between the fracture type (AO type A3) and longer time to fracture union.
Acute viral respiratory infections (AVRI) are a leading cause of morbidity and mortality among all age groups globally. Except for Influenza virus and Respiratory Syncytial virus, mostly viral aetiology of AVRI remains undiagnosed. Lately, human coronaviruses (HCoVs) have emerged as an important aetiology of AVRI. A laboratory based retrospective cross sectional study was conducted in which respiratory samples (throat swabs) of patients (n = 864), with Influenza negative SARI, of all age groups between Jan 2011-Dec 2012 were tested for HCoVs including MERS-CoV using Conventional and real time PCR assays. The prevalence of HCoV among SARI cases was 1.04% (9/864) [95% CI: 0.36-1.72]. Of these four (44.44%) were identified as HCoV OC43, three (33.33%) as HCoV NL63 and two (22.22%) as HCoV 229E. No HCoV HKU1 was detected. The samples were also negative for SARS-CoV and MERS-CoV. The results of this study documents low prevalence of human coronaviruses in SARI cases in south western India and the absence of highly pathogenic human coronaviruses. As the study included only SARI cases the prevalence reported could be an under estimate when it is extrapolated to community.
Kyasanur Forest disease (KFD) is a tick-borne, acute, febrile viral illness endemic in southern India. No major studies have been done to understand the adaptive immune response during KFDV infection in humans. In this study, KFDV-positive patients were prospectively enrolled, and repeated peripheral blood collections were performed. Clinical and virologic characterization of these samples is reported along with phenotypic analysis of cellular immunity and quantitation of humoral immunity. We noted robust T and B cell responses, particularly of CD8 T cells, during KFDV infection in most of the patients. Virus clearance from the blood coincided with peak CD8 T cell activation and the appearance of KFDV-specific IgG. Increased frequency of plasmablasts and very few activated B cells were observed in the acute phase of KFD infection. Notably, only humoral immunity and activated B cell frequency in the acute phase correlated with prior KFDV vaccination, and only with 2 or more doses. This novel work has implications in KFD vaccine research as well as in understanding the pathogenesis.
Background: Cervical cancer is the second commonest cancer among Indian women and its association with human papilloma virus (HPV) is well established. This preventable cancer accounts for the maximum number of cancer related deaths among rural Indian women. Unlike in developed countries there are no organized cervical cancer screening programmes in India due to lack of resources and manpower. Objective: To detect genital HPV infection using urine samples among asymptomatic rural women in the age group of 18-65 years. Materials and Methods: The study area chosen was Perdoor village in Udupi Taluk, Karnataka State and all the women in the age group of 18-65 years formed the study cohort. A cross sectional study was conducted by house visits and 1,305 women were enrolled in the study. After taking written informed consent a data sheet was filled and early stream random urine samples were collected, transported to a laboratory at 4 O C and aliquoted. Samples were tested using nested HPV PCR with PGMY09/11 and GP5+/6+ primers. Positive cases were genotyped by sequence analysis. Results: Study participants included 1,134 sexually active and 171 unmarried women with a mean age at marriage of 22.1 (SD=3.9) years. Study area showed high female literacy rate of 86.6%. Five urine samples tested positive for HPV DNA (0.4%). Conclusions: We found very low genital HPV infection rate among women from monogamous community. This is the first major population based study carried out among asymptomatic rural women to detect genital HPV infectio from Karnataka using urine samples.
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